Pfizer’s Paxlovid, an oral antiviral approved by the US FDA in December, has shown 90% efficacy in preventing mortality among those who take it in the first few days of infection.

A Medicines Patent Pool (MPP) announcement Thursday that it has signed agreements with 35 companies to manufacture generic versions of Pfizer’s life-saving COVID-19 Paxlovid treatment for distribution in 95 low- and middle-income countries came fire almost immediately from medicines access groups as too little, too late. 

The MPP-brokered sublicences follow on from an agreement between MPP and Pfizer in November 2021 to supply generic versions of Pfizer patented main drug ingredient, nirmatrelvir, at cost, to countries that represent about 53% of the world’s population.

However, activists quickly slammed with the new accord – saying that it would take up many months to actually set up the generic production lines of the game-changing oral drug, which in clinical trials, reduced COVID mortality by 90% among high risk groups.  

Mapping of the MPP-brokered licenses awarded for manufacture of a generic version of Paxlovid

In a joint letter to Pfizer CEO Albert Bourla, delivered Wednesday, a consortium of 100 activist groups, including Amnesty International and Oxfam, said that Pfizer should immediately dedicate two-thirds of the company’s available patented drug supply to low- and middle-income countries, “where there is a proportionate need.” 

“At present, Pfizer has preferentially sold all of its Paxlovid doses from the first half of 2022 to a handful of high-income countries, and has tentatively promised to supply only 10 million courses of treatment of LMICs,” stated the Health Global Access Project (Health Gap), one of the signatories to Wednesday’s letter,  in a follow-up blog posted online just after the MPP announcement.

The activists also have slammed the still high price of the new drug in upper-middle and high income countries, saying that this also creates barriers to access. The United States is paying about $530 a day for a five-day course, although Pfizer has committed to a 3-tiered pricing system with lower costs to less affluent countries. 

 “This announcement will do nothing to eliminate the monopoly Pfizer maintains over unlicensed countries – all high-income and almost all upper-middle income countries, representing 47% of the world’s population and historically experiencing the highest rates of COVID-19 infection,” added Brook Baker, Health Gap Senior Policy Analyst and a Professor at Northeastern University School of Law.  

MSF –  A ‘positive step’ forward 

Médecins Sans Frontières sounded a more positive note,  however, saying that the Pfizer agreement with 35 generics manufacturers in 12 countries represents a “positive step toward addressing the ongoing access challenges for this COVID treatment.  However, the limitations of the deal remain concerning.”

“The limited global supply from the US corporation Pfizer has so far largely been bought up by a number of high-income countries. It is estimated that generic manufacturers will not be able to bring supply to the market until 2023,” stated MSF.

Replying to the criticism, an MPP spokesperson stressed that the new agreement “includes all low and lower-middle-income countries as well as some upper-middle income countries in Sub-Saharan Africa that have transitioned to upper-middle-income status in the past five years.

The 53% of the world’s population covered by the licenses, “which is equivalent to about 4.1 billion people. As with all our licences we will continue to explore opportunities to broaden geographic scope, where possible,” the MPP spokesperson added.

Design of MPP agreement  

According to MPP, the non-exclusive sublicence deals will allow generic manufacturers to produce the raw ingredients for Paxlovid’s main active ingredient, nirmatrelvir, and/or the finished drug itself, which is co-packaged with a common HIV drug, ritonavir. 

It said that six companies will focus on producing the drug substance, nine companies will produce the finished drug product and the remainder will do both. 

The manufacturers are based in 12 countries including: Bangladesh, Brazil, China, Dominican Republic, Jordan, India, Israel, Mexico, Pakistan, Serbia, Republic of Korea, and Vietnam. 

“A licence has also been offered to a company in Ukraine, the offer will remain available to them as they are not able to sign due to the current conflict,” MPP said.

The deal signed between MPP and Pfizer in November 2021 established the terms and conditions, for the generic licenses, MPP added. Following that, “The requests for sublicences from generic producers were reviewed by MPP and presented to Pfizer,” for its approval – one of the conditions of the sale. 

Pfizer will not receive royalties from sales of nirmatrelvir from the MPP-negotiated sublicensees for as long as COVID-19 remains classified as a Public Health Emergency of International Concern by the World Health Organization, MPP added. 

Following the pandemic period, sales to low-income countries will remain royalty free, lower-middle-income countries and upper-middle-income countries will be subject to a 5% royalty for sales to the public sector and a 10% royalty for sales to the private sector.

“Nirmatrelvir is a new product and requires substantial manufacturing capabilities to produce, and we have been very impressed with the quality of manufacturing demonstrated by these companies,” said Charles Gore, MPP Executive Director. “Furthermore, 15 companies are signing their first licence with MPP, and we warmly welcome our new generic manufacturing partners.”

“We have established a comprehensive strategy in partnership with worldwide governments, international global health leaders and global manufacturers to help ensure access to our oral COVID-19 treatment for patients in need around the world, said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “The MPP sublicensees and the additional capacity for COVID-19 treatment they will supply will play a critical role to help ensure that people everywhere, particularly those living in the poorest parts of the world, have equitable access to an oral treatment option against COVID-19.”

Image Credits: Pfizer , Medicines Patent Pool .

A month after a fourth dose of the Pfizer or Moderna vaccines was administered to hundreds of people in an Israeli clinical trial, authors of the new study on the extra booster say it provides “little protection, if any, from infection by COVID-19 among vaccinated young and healthy individuals in comparison to those vaccinated with only a third dose.”

Result of the open-label study, conducted at Israel’s Sheba Medical Center, were published Wednesday evening in the New England Journal of Medicine as a correspondence.

The findings contradict statements made by Pfizer CEO Albert Bourla over the weekend that a fourth booster dose could necessary for most people, due to waning immunity. Bourla made the statement as Pfizer seeks quick US Food and Drug Administration approval of a fourth dose, effectively a second booster, for people 65 and older.

The new Sheba study included approximately 600 volunteers, among them 270 who received a fourth shot of either the Moderna or Pfizer vaccine. All of the volunteers had received three shots of the Pfizer vaccine prior to the trial.

Sheba’s Professor Gili Regev-Yochay, lead author of the study, said in a statement that COVID infection rates among four-time vaccinated individuals were only slightly lower than those in the control group. However, she added that the fourth jab did provide moderate protection against symptomatic infection among young and healthy individuals, in comparison to those who had only received three jabs.

“We found no differences, both in terms of IgG antibody levels and in terms of neutralizing antibody levels,” added Regev-Yochay, referring to the impact of the fourth jab on the study group in comparison to the control.

“It should be emphasized that the third dose is extremely important for anyone who has not yet contracted COVID-19,” Regev-Yochay stressed, “and the fourth dose is most likely important for populations with risk factors, for which a fourth vaccine would protect from serious illness.”

The NEJM correspondence, however, said that the fourth dose was “immunogenic, safe and somewhat efficacious”, adding that “our results suggest that maximal immunogenicity of mRNA vaccines is achieved after three doses and that antibody levels can be restored by a fourth dose.”  The researchers added that they observed “low vaccine efficacy against infections in health care workers, as well as relatively high viral loads suggesting that those who were infected were infectious.”

Bourla: Fourth shot ‘necessary’

The release of the data comes at an awkward time for Pfizer, after a weekend when Bourla said in an interview with CBS’s Face the Nation that a fourth COVID-19 shot would be “necessary” for most people to prevent future infection.

Pfizer CEO Albert Bourla in a CBS interview on March 13, 2022.
Pfizer CEO Albert Bourla in a CBS interview on March 13, 2022.

“Right now, the way that we have seen, it is necessary, a fourth booster right now,” Bourla said in the interview. “The protection that you are getting from the third, it is good enough, actually quite good for hospitalizations and deaths. It’s not that good against infections, but doesn’t last very long.”

While Bourla said Pfizer had submitted data on the efficacy of the fourth shot to the US FDA, the data has not yet been publicly released.

The US Centers for Disease Control and Prevention currently recommends three jabs for everyone age 12 years and up, and two shots for children between the ages of five and 11. Individuals who are immunocompromised are encouraged to get an extra dose.

Fourth dose still protects against severe infection, separate study found

A separate Israeli study published, on February 1 by the Israeli Health Ministry, offered somewhat contradictory results to the Sheba findings – although the Ministry of Health study focused only on older people.  That study, released on the pre-print biomedical website MedRXiv, found that rates of confirmed COVID-19 infection, as well as severe illness, were lower following a fourth dose, when compared to only three doses.

Specifically, the team looked at data from 1,138,681 persons aged over 60 years and eligible for the fourth dose between January 15 and 27, 2022 – the height of the Omicron wave in Israel. They compared the rate of confirmed COVID infections and severe COVID illness between those who took a fourth jab at least 12 days earlier and those who only had three doses, or alternatively those who became ill less than a week after receiving the fourth dose.

“The rate of confirmed infection was lower in people 12 or more days after their fourth dose than among those who received only three doses and those 3 to 7 days after vaccination by factors of 2.0 and 1.9, respectively. The rate of severe illness was lower by factors of 4.3 and 4.0,” the authors wrote.

‘Vaccines don’t prevent infection’

Professor Cyrille Cohen, head of the immunology lab at Bar-Ilan University, said that the findings from the Sheba study are not surprising; “the vaccines are not good enough to prevent infection, and even more so with the Omicron variant,” he said.

However, like Regev-Yochay, Cohen stressed that there is a growing body of data that shows there remains a substantial difference in the levels of protection acquired by people who are vaccinated with two doses and those who get three doses, when it comes to developing severe disease.

“Look at the ratio between people age 60 who got three doses and people that were not vaccinated and got two doses. Even with Omicron, the third dose can reduce the chance of developing severe disease by a factor of four or five and for people above 60 that number becomes 10 to 20,” Cohen said.

He also noted that a fourth dose also may help the most vulnerable, noting that today, the serious cases in Israel still tend to be older people with comorbidities or unvaccinated people.

“Based on that, a fourth dose for selected populations might demonstrate a benefit,” he said.

When asked about Bourla’s statement, Cohen said “it was not clear” and that perhaps the Pfizer CEO was referring to people receiving a shot of the Omicron-adapted vaccine, for which data has not yet been released. A multi-country clinical trial of that vaccine is now underway, including a trial arm in Israel.

“I am personally extremely curious to see those results,” Cohen said.

Image Credits: Screenshot.

Attacks on health facilities appear to be part of a deliberate war strategy in Ukraine and other recent conflicts, according to the head of the World Health Organization (WHO) health emergencies programme.

The WHO has verified 43 attacks on Ukrainian health facilities since Russia’s invasion on 24 February – and it expects further attacks as over 300 health facilities in conflict areas or under Russian control and a further 600 facilities within 10 kilometres of conflict.

But WHO Director-General Dr Tedros Adhanom Ghebreyesus told a media briefing on Wednesday that there had also been 46 attacks on health facilities worldwide since the start of 2022, and people caught in conflicts in Tigray, Yemen and Syria were in extreme need of humanitarian assistance. 

Dr Mike Ryan, WHO Executive Director of Health Emergencies Programme, said that in these conflict zones, attacks on health facilities appeared to be deliberate – in complete violation of international law.

“We have never seen this rate of attacks on health care, and health care becoming a target in these situations. It’s becoming part of the strategy and tactics of war and it is entirely unacceptable,” said Ryan.

“Under international humanitarian law. conflicting parties are actually instructed to specifically take measures to avoid attacking or inadvertently destroying or hurting health workers or health facilities. They don’t bear responsibility not just to not attack. They actually bear responsibility to ensure that they don’t attack to identify those facilities, to deconflict those facilities and to ensure that they do not, as part of their prosecution of war, attack those facilities,”  he added.

Dr Mike Ryan, WHO Executive Director of Health Emergencies Programme.

Multiple conflicts out of the global eye

“Although Ukraine is the focus of the world’s attention, it’s far from the only crisis to which WHO is responding,” said Tedros.

“In Yemen, roughly two-thirds of the population – more than 20 million people – are estimated to be in need of health assistance. In Afghanistan, more than half the population is in need, with widespread malnutrition and a surge in measles among many other challenges. 

“And in Ethiopia, six million people in Tigray have been under blockade by Ethiopian and Eritrean forces for almost 500 days, sealed off from the outside world. There is almost no fuel, no cash and no communications. No food aid has been delivered since the middle of December and 83% of the population is food insecure,” said Tedros, who is from Tigray and added his family and friends were affected by the blockade.

Aid to Ukraine – but little for Tigray

WHO Director-General Dr Tedros Adhanom Ghebreyesus.

The WHO has been able to deliver about 100 metric tonnes of supplies to Ukraine, including oxygen, insulin, surgical supplies, anaesthetics and blood transfusion kits; oxygen generators, electrical generators and defibrillators.

However, it had only received $8million of the $57.5 million it needed to support Ukraine.

In contrast, however, it had only been able to airlift 33 metric tonnes of medicines and other supplies to Tigray in December – enough for 300,000 people – after being denied access to the territory since last July.

“We estimate that 2,200 metric tonnes of emergency health supplies are needed to respond to urgent health needs in Tigray,” said Tedros.

Treatment for 46,000 Tigrayan people living with HIV has been abandoned, as has treatment for people with cancer, diabetes, hypertension and tuberculosis.

“The situation in Tigray is catastrophic. The blockade on communications, including on journalists being able to report from Tigray, means it remains a forgotten crisis. Out of sight and out of mind,” added Tedros.

“Just as we continue to call on Russia to make peace in Ukraine, so we continue to call on Ethiopia and Eritrea to end the blockade, the siege, and allow safe access for humanitarian supplies and workers to save lives,” said Tedros.

Global COVID-19 cases rise again

Meanwhile, after weeks of global decline COVID-19 cases are on the rise again, especially in parts of Asia. 

“In the last week, we saw an 8% increase in cases detected with more than 11 million cases reported to WHO despite a significant reduction in testing that’s occurring worldwide,” said WHO COVID-19 lead Dr Maria van Kerkhove.

She ascribed the increase to the spread of the Omicron variant – particularly the BA.2 lineage which is “the most transmissible variant we have seen of the SARS Co-V2 virus to date” – in a context where restrictions were being lifted globally.

Ryan added that the virus would move from one “pocket of susceptibility” where immunity was waning to another.

“The likelihood is that this virus will echo around the world,” said Ryan. “It will pick up pockets of susceptibility and will survive in those pockets for months and months until another pocket of susceptibility opens up,” said Ryan. 

“This is how viruses work. They establish themselves within a community and they will move quickly to the next community that’s unprotected. If communities around the virus are well protected, the virus can sustain itself, even in small communities. It can stay there, it can rest there, and then wait until susceptibility grows.”

Image Credits: Markus Spiske/ Unsplash.

WTO members last week in session at the TRIPS Council, which has been debating a controversial proposal for an IP waiver on COVID products for over a year.

The World Trade Organization’s (WTO) Director-Genera, Dr Ngozi Okonjo-Iweala has “warmly welcomed” the breakthrough reached this week over a waiver on intellectual property for the production of COVID-19 vaccines.

“This is a major step forward and this compromise is the result of many long and difficult hours of negotiations. But we are not there yet. We have more work to do to ensure that we have the support of the entire WTO Membership,” said Okonjo-Iweala, in a statement on Wednesday.

The agreement reached between the European Union, India, South Africa and the United States – referred to in some quarters as “the Quad” – still needs to be put to all 164 WTO members, which typically decides by consensus.

However, the compromise now has good chances of being approved since EU countries had been the major opponents to the proposal by South Africa and India, submitted in October 2020, to waive IP on COVID-19 vaccines and other pandemic-related health products for the duration of the pandemic. 

Major concessions

South Africa and India had to make major conceessions  – both narrowing the waiver to only vaccines, as well as narrowing the list of countries that would be eligible to take advantage of the waiver on patents and other IP.     

“My team and I have been working hard for the past three months and we are ready to roll up our sleeves again to work together with the TRIPS Council Chair Ambassador Lansana Gberie (Sierra Leone) to bring about a full agreement as quickly as possible. We are grateful to the four Members for the difficult work they have undertaken so far,” said Okonjo-Iweala.

The WTO’s Ministerial Council (MC12), postponed from late November to the week of June 13, could potentially approve the waiver move – although the date of that meeting has also been cast into doubt due to the recent outbreak of war in the Ukraine. 

However, the draft text of the proposed compromise, published by STAT News Tuesday evening, has elicited dismay from both health activists and the pharmaceutical industry – for not going far enough, or for going too far.

Restricted to vaccines and certain developing countries

In essence, the compromise does three things:

  • Most critically, the new waiver would allow developing countries to not only manufacture, but also to export, generic versions of COVID vaccines that are still under patent protection. Currently, Article 31.f of the WTO Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS) agreement restricts such generic manufacture to health products that are “predominantly for the supply of the domestic market” – leaving low-income countries with no manufacturing base unable to import cheaper generic versions of products from abroad. 
  • However, the waiver would be limited to countries that exported less than 10% of the world’s vaccines in 2021. That effectively excludes well-established manufacturers in China, but not India, from waiver eligibility. 
  • In contrast to the original Indian-South African proposal, the new IP flexibilities are restricted to COVID vaccines, thus excluding COVID treatments such as new antivirals that are particularly important for countries with low vaccination rates, as well as tests, personal protective equipment (PPE) and other pandemic-related goods.

Adam Hodge, spokesperson for US Trade Representative Ambassador Katherine Tai, said late Tuesday that the “compromise outcome that offers the most promising path toward achieving a concrete and meaningful outcome” after a “difficult and protracted process”.

He and others cautioned that details of a final text were yet to be concluded. 

“While no agreement on text has been reached and we are in the process of consulting on the outcome, the US will continue to engage with WTO Members as part of our comprehensive effort to get as many safe and effective vaccines to as many people as fast as possible,” added Hodge.

The informal discussions, led by the WTO Secretariat, have been trying to break the deadlock between the India-South Africa waiver proposal (supported by the Africa and Least Developed Nations groups and others) and the EU’s counter-proposal.  

India-South Africa proposal had sought a broad waiver on all vaccines, tests and treatments, while the EU had pushed for technical modifications in the existing TRIPS rules. 

Medicines access activists and pharma leaders both express dismay 

Both activists and industry reacted with dismay to news of the proposed agreement. For example, the US-based consumer advocacy group, Public Citizen, called on WTO member states to reject the proposal.

“Among its key limitations: the proposal appears to cover only vaccines (not tests and treatments), cover only patents (not other important intellectual property barriers), be limited geographically, and further undermine current WTO flexibilities for compulsory licenses,” according to Melinda St Louis, director of Public Citizen’s Global Trade Watch division.

“It would be a mistake for WTO members to prematurely agree to a weakened waiver that provides political cover to the US and EU while not making any meaningful difference in increasing access to vaccines, tests and treatments. No waiver is better than a weak waiver designed solely to save face,” added St Louis.

Knowledge Ecology International also expressed disquiet, saying that the waiver may even restrict certain flexibilities that are already allowed by Article 31 of the WTO Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS), regarding a country’s rights to manufacture and export generic versions of drugs or vaccines during a health emergency. 

“Countries are required to follow Article 31 of the TRIPS [agreement], which of course, is an existing and not a new flexibility, but with ‘clarifications’,” noted KEI’s Director, James Love.

However, those “clarifications”, also come with new obligations that could make Article 31 “more restrictive and burdensome”, such as a new obligation for a country to identify all of the patents to which it is applying an IP waiver, and to notify the WTO of its use of the waiver –  something not required for the issuance of compulsory licenses in general.  

On the other hand, the draft agreement makes a first-ever reference to a 2005 WHO/UNDP guidance on payments by developing countries to the original patent-holder, which embraces the concept of “tiered royalties”, based on a country’s ability to pay, and authored by Love himself.

Pharma says agreement sends ‘wrong signal’

Meanwhile, the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) said that “weakening patents now when it is widely acknowledged that there are no longer supply constraints of COVID-19 vaccines, sends the wrong signal”. 

“​​When the IP TRIPS Waiver was first proposed in 2020, it was to the wrong solution to the problem of scaling up manufacturing of potential COVID-19 vaccines which at the time had not yet even been authorized,” said the IFPMA.

“Now the problem of supply has been addressed thanks to unprecedented collaboration involving companies from industrialized and developing countries, the TRIPS Waiver is not only the wrong solution, it is also an outdated proposal, that has been overtaken by events.”

It added that the TRIPS waiver proposal is “political posturing that are at best a distraction, at worse creating uncertainty that can undermine innovation’s ability to respond to the current and future response to pandemics”. 

“The current proposals should be shelved; and the focus should be directed, to admittedly more difficult actions that will change lives for the better: supporting country readiness, contributing to equitable distribution, and driving innovation,” the IFPMA concluded.

The final text of any agreement would first need to be approved by the WTO TRIPS Council, and then go before the MC12 for final approval. 

The TRIPS Council last met on 9-10 March, but at the time failed to reach a compromise – although some sources noted that the were close to agreement as the “Quad” of India, South Africa, the United States and the EU scrambled to reach a deal.

According to a WTO statement on 10 March, the TRIPS Council had agreed to keep the agenda item on the IP waiver open – so as to enable the council to be “reconvened at short notice if substantial progress is made in the high-level talks”.  TRIPS Council approval would pave the way for a consensus agreement at the WTO’s Ministerial meeting, MC12. 

Mariupol Regional Hospital before it was bombed

Health workers, patients and civilians have been held hostage at the Mariupol regional intensive care hospital in Ukraine by Russian troops since Monday morning, according to the Media Initiative for Human Rights (MIHR).

Russian soldiers are using the hospital as a base to attack Ukrainian forces, and using the hostages as “human shields” according to MIHR, a respected human rights monitoring group in Ukraine.

“We received information from a doctor from the hospital. We can’t name him because of the threat to him. More information will be available after the person is safe,” the MIHR reported on its Facebook page.

Pavlo Kyrylenko, head of the Donetsk regional administration, also reported the hostage situation on his Telegram account.

Kyrylenko reported that a hostage had told him: “It is impossible to leave the hospital. There is heavy shelling. We sit in the basement. Cars have not been able to drive into the hospital for two days. High-rise buildings are burning around… Russians rushed 400 people from neighbouring houses to our hospital. We can’t leave. “

While the 550-bed tertiary hospital, the biggest in the Donetsk region, has suffered extensive damage, health workers have continued to attend to patients from the basement.

“I appeal to international human rights organizations to respond to these vicious violations of the norms and customs of war, to these egregious crimes against humanity,” said Kyrylenko.

Humanitarian groups have been appealing for days for a safe passage corridor to and from Mariupol. Some private cars were finally able to leave the city on Monday and Tuesday, the first time in 10 days. But Russian troops that have beseiged the city on all sides have not allowed relief workers to bring in desperately needed medical supplies, food or water.

Last week, Russian troops bombed the Mariupol maternity hospital, reportedly killing at least three people. A pregnant woman evacuated from the hospital and her baby later died from their injuries.

Mariupol’s deputy mayor, Sergey Orlov, told France24 on Tuesday that at least 2,358 people had been killed during the 11-day siege of the south-eastern city, and he had been fielding desperate calls from people trapped in basements without food or water.

‘Act of unconscionable cruelty’

The World Health Organization (WHO) has verified 31 attacks on health facilities between the start of the Russian invasion on 24 February and 11 March, resulting in 12 deaths and 34 injuries, of which 8 of the injured and 2 of those killed were health workers. 

“We call for an immediate cessation of all attacks on health care in Ukraine. These horrific attacks are killing and causing serious injuries to patients and health workers, destroying vital health infrastructure and forcing thousands to forgo accessing health services despite catastrophic needs,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus,  UNICEF Executive Director Catherine Russell and UNFPA Executive Director Dr Natalia Kanem, in a joint statement on Sunday.

“To attack the most vulnerable – babies, children, pregnant women, and those already suffering from illness and disease, and health workers risking their own lives to save lives – is an act of unconscionable cruelty,” they added.

“We must be able to safely deliver emergency medical supplies – including those required for obstetric and neonatal care – to health centers, temporary facilities and underground shelters.”

Intentionally attacking health facilities is prohibited under international humanitarian law. 

Unusual position of surrogates

Since the start of the war, more than 4,300 Ukrainian women have given birth, and  80,000 others are expected to give birth in the next three months. 

“Oxygen and medical supplies, including for the management of pregnancy complications, are running dangerously low,” according to the three leaders.

“Many pregnant women may need health care, medication and assistance on a daily basis or when complications with pregnancy occur. When medical facilities are not accessible, are destroyed, or health care personnel and medical product are scarce or unavailable, maternal health can be endangered,” according to Eszther Kisomodi and Emma Pitchford, the chief executive and executive editor respectively of the journal, Sexual and Reproductive Health Matters.

They also warned that many pregnant women might be in “particular and unusual situations” as Ukraine “is an international surrogacy hub, one of only a handful of countries in the world that legally allows foreigners to enter into surrogacy arrangements”.

https://twitter.com/thedalstonyears/status/1501861609446289410

“Being a surrogate is a job in Ukraine for many women, but not one that they can quit, or even put on hold. Very serious questions occur for all parties in this arrangement – for the pregnant women, the newborn child and the intended parents.”

The authors also highlight the precarious position of people with disabilities who cannot move easily, LBGTQ people in the face of hostile Russian forces, and people living with HIV in Ukraine, which has the second-highest infection rate in Europe.

The COVID-19 pandemic has killed 6 million people so far, but the next pandemic threat could emerge unnecessarily from pathogen resistance to life-saving antibiotics and other anti-microbial drugs. What steps do we need to take now to head off this growing threat?

For decades, antibiotics have been hailed as “wonder drugs” for their ability to turn life-threatening infections into treatable conditions.  By one estimate, antibiotics have extended average human life expectancy by more than 20 years since their discovery almost a century ago. 

But today, we are on the brink of losing this powerful tool – a warning that Alexander Fleming conveyed in his Nobel acceptance speech in 1945 for the discovery of penicillin, the world’s first broad-spectrum antibiotic: “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body. The time may come when penicillin can be bought by anyone in the shops”.

He challenged listeners with a hypothetical illustration: “Mr X has a sore throat. He buys some penicillin and gives himself, not enough to kill the streptococci but enough to educate them to resist penicillin. He then infects his wife. Mrs X gets pneumonia and is treated with penicillin. As the streptococci are now resistant to penicillin the treatment fails. Mrs X dies. Who is primarily responsible for Mrs X’s death? Why, Mr X whose negligent use of penicillin changed the nature of the microbe. Moral: If you use penicillin, use enough.”

 Sadly, this is not an imaginary exercise. It’s a grim reality. It’s the world we’re living in today. In a biologically dictated race to survive, bacteria evolve and eventually become strong enough to defeat the world’s current arsenal of antibiotics.  People acquire infections that can’t be treated.  The result is the antimicrobial resistance (AMR) crisis the world faces today. 

AMR: The stealth and silent pandemic

The most comprehensive estimate to date, recently published in The Lancet, shows that antimicrobial-resistant bacteria may have directly accounted for 1.27 million deaths in 2019. A further 4.95 million deaths were associated with AMR, making it a stealthy and silent pandemic.

How have we failed to heed Fleming’s warning about AMR?

There are many forces driving AMR. Perhaps one of the most important is the rampant over-prescription of antibiotics. According to the US Centers for Disease Control and Prevention (CDC), nearly one-third of all antibiotics prescribed in the US are unnecessary.  In India, the consumption of antibiotics more than doubled between 2000 and 2015, in part because these drugs are widely available over-the-counter without a doctor’s prescription. 

But there are ways to slow the march of AMR. Beyond promoting better stewardship for the appropriate use of antibiotics, reducing the risk of AMR also requires higher awareness among both doctors and patients; better access to diagnostics to guide the prescription of the right antibiotic at the right time; better sanitation measures; responsible manufacturing; and better surveillance by governments. But along with these steps, we must restock the antibiotics R&D pipeline with novel ones that have a better chance of overcoming current resistance.

Clearly, no single player or sector can tackle AMR alone. The scale of the challenge may seem daunting, but it has certainly galvanized action. As chair of the AMR Industry Alliance, the world’s largest life-sciences coalition gathering more than 100 biotechnology, diagnostics, generic and large research-based pharmaceutical companies and associations, I witness how every life-sciences industry sector contributes to co-creating solutions that make a difference.  

Industry’s fight against AMR

In February, the Alliance released its latest Progress Report reflecting the work the life-sciences industry is undertaking to address the threat of AMR, across four different areas: research and science, access, appropriate use, and manufacturing and the environment.  The report, based on independent, quality-assured research conducted by the not-for-profit policy research organization RAND Europe, analyses data from a survey of Alliance member companies.

It found that about four out of five responding companies are actively engaged in promoting better stewardship of antibiotics and the appropriate use of these drugs to guard against over-prescription. An even larger proportion – 85 percent of responding companies – are making significant contributions to the responsible manufacturing of antibiotics.

The report also found that the private sector remains one of the key funders of AMR-related R&D, with at least $1.8 billion invested by Alliance members. Alliance members contributed to R&D on 93 products or technologies spanning 54 antibiotics and antifungals, 12 vaccines, 13 diagnostic platforms and assays and 14 non-traditional or other products. Alliance members continue to conduct R&D on AMR priority pathogens. However, these funding levels are at risk given challenging market conditions for antibiotic development. This is where continued dialogue between industry and wider stakeholders will be needed to ensure a scalable and sustainable incentive system.

Four priorities for collaborative action

 While industry is making progress in many areas, contributions from and collaboration among all stakeholders is needed. There are four key priorities where AMR Industry Alliance members see scope for action:

 First, to support research and science, the AMR Industry Alliance calls for greater public-sector investment in R&D and a clinical trial infrastructure to promote better innovation in the development of new antibiotics. Continued public-private collaboration between and among universities, hospitals and pharmaceutical companies is also essential and should be expanded to include more biotech, diagnostics and generics manufacturers.

To create the market conditions needed to encourage the pipeline, particularly the later and more resource-intensive stages of clinical research, governments should implement so-called “pull” incentives. New antibiotics are typically locked away and reserved for when existing antibiotics become ineffective against antimicrobial-resistant infections. Pull incentives correct this marketplace flaw by rewarding new antibiotics according to their value to society, not merely how many prescriptions are written.  This enables companies to recover their investments, drawing even more financial and scientific resources into the battle against AMR.

Second, to make access more equitable, especially in low- and middle-income countries, all stakeholders should work together to improve the way antibiotics are ordered, purchased and supplied, including forecasting demand for key antibiotics, as well as the tendering process. This will strengthen manufacturing capacity and supply chains and broaden distribution channels to create a sustainable supply of quality-assured antibiotics.  These efforts should be supplemented by awareness campaigns that educate patients and the medical community about substandard or fake products in the marketplace.

Third, to encourage appropriate use of antibiotics and cut down on over-prescription, governments, health care providers and pharmaceutical and diagnostics companies need to work together on communications campaigns that raise awareness, reduce sales of antibiotics without prescriptions and curb the overuse of critical antibiotics by following the guidance provided by the WHO AWaRe classification.  Better surveillance of AMR through improved data collection and increased public reporting of infection rates and antibiotics use is also essential. 

Fourth, to promote responsible manufacturing, stakeholders should also work together to develop and implement international standards for responsible antibiotics manufacturing. The Alliance and our members have been actively working towards this objective, and in the absence of such standards, in 2018, established the Common Antibiotic Manufacturing Framework (CAMF), a set of guidelines to assess risk and reduce antibiotic emissions across global supply chains, as well as a list of Predicted No-Effect Concentrations (PNECs) to serve as discharge targets for manufacturers. Our Progress Report shows that Alliance members are acting on this guidance even as we pursue standards.

Silent no more

We still have a lot of ground to cover. In the six years remaining until the centenary of the discovery of penicillin, we need a strong showing of collective action to spur and sustain responsible stewardship and innovation against AMR. By doing so, we can make sure that future generations can continue to rely on these life-saving tools.

AMR won’t race across the world at the same speed as COVID-19, but its effects will be equally devastating. After far too much silence on AMR, the alarms bells are now ringing.  We can’t afford not to respond.

Thomas Cueni, director general of the IFPMA

Thomas B. Cueni is chair of the AMR Industry Alliance and the Director-General of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA).

 

Image Credits: IFPMA .

Unconscious and intubated Covid-19 patients are treated in Vila Penteado Hospital’s ICU, in Sao Paulo, Brazil.

The first session of the newly constituted Intergovernmental Negotiating Body (INB) to draft a “pandemic preparedness instrument” for the World Health Organization (WHO) began on Monday.

The six-member body, representing all WHO regions, is made up of Precious Matsoso (South Africa), Roland Driece (the Netherlands), Ambassador Tovar da Silva Nunes (Brazil), Ahmed Salama Soliman (Egypt), Kazuho Taguchi (Japan) and Viroj Tangcharoensathien (Thailand).

The two-day session will elect two co-chairs, as well as agree on the working methods and timelines of body “based on the principles of inclusiveness, transparency, efficiency, Member State leadership and consensus”, according to the agenda.

Meanwhile, almost 200 civil society leaders have asked the six negotiators to protect the process from any “undue influence of the private sector and its powerful lobbyists”.

In an open letter addressed the six negotiators, the leaders have asked the INB to pay attention to a number of issues including:

  • The multiple determinants of potential future pandemics, including the inherent injustice and structural inequities exacerbated by such crises
  • The interconnected dynamics of issues, including the unsustainable food production and livestock breeding, wildlife trading, resource-intensive lifestyles and consumption, destruction of ecosystems, antimicrobial resistance and soaring figures of cancer
  • The state of universal public health systems and their workforce 
  • Incoherent policymaking by Member States and the lack of international cooperation
  • Ensuring more inclusive engagement in the treaty-making process that balance the Member State-driven delicate diplomatic process and protect it from the undue influence of the private sector and its powerful lobbyists.

The letter has been facilitated by the Geneva Global Health Hub (G2H2), as a service to its members involved in this process.

Image Credits: Adnan Abidi/Flickr, Ninian Reid/Flickr.

A member of a Community Action Cell speaks to a woman outside her home in Kinshasa about the COVID-19 vaccine.

With fewer than 1% of its 90 million citizens vaccinated against COVID-19, the Democratic Republic of Congo (DRC) has resorted to training teams of “rumour-busters” to tackle misinformation about the virus in order to encourage more people to get the vaccine.

David Olela, communications lead for the DRC health ministry’s vaccination programme,  admits that his government had been “stuck”, with “no idea how to combat both the pandemic and the disinformation at the same time” until it got help from “infodemic experts”.

Health workers, religious and community leaders and journalists spread across the DRC’s vast landmass of around 2.3 million square kilometres have been trained to help combat misinformation.

“Having a local team trained in rumour management has helped us turn an anti-vaccine narrative into a pro-vaccine one,” says Olela, whose ministry is being supported by partners including the World Health Organization (WHO) and UNICEF. 

Rumours about pork in vaccines

Imam Famba Ali Huseini, leader of the Usoke Central Mosque in Kinshasa, is one of 30 imams who has been trained in the capital city.

“At the start of the pandemic, we were inundated with rumours and disinformation on COVID-19 and vaccines,” says Huseini. “In Kinshasa’s Muslim community, people feared the vaccine. Some thought Africans were being used as guinea pigs, and that the vaccines were made with pork gelatine.”

Part of their training involved a doctor explaining how the vaccine was made to show that no pig gelatine was involved. But more impressive for Huseini was learning that people in Muslim countries such as Saudi Arabia and Indonesia had accepted the vaccine. Around 10% of DRC citizens are Muslim.

More than 600 health workers have been trained in identifying and refuting myths surrounding the COVID-19 vaccine. Question-and-answer sessions on rumour refutation have also been organized in the national parliament, before 300 national and provincial representatives.

In addition, 144 media professionals have been trained in fact-checking and source reliability. This includes Congo Check, an online fact-checking agency, which has been exposing fake news about the pandemic and vaccines.

Hesitation to call out vaccine ‘hesitancy’

While none of the international agencies working in the DRC is willing to ascribe the low vaccination rate to “vaccine hesitancy”, it is evident that the country is facing a huge struggle to win people over to vaccines.

A survey conducted in November involving 74,388 people found that respondents were split equally between those that supported vaccinations and those who didn’t (see above).

For those who are not yet vaccinated, the main reason (28%) was that they “don’t believe in them”. The second most popular reason was that the person felt healthy (18%), followed by fear about vaccine side effects (13%).

But even the survey itself was met with apathy. It had tried to solicit the views of almost two million people and only got a 4% response.

In late 2020, an online survey of 4131 people conducted by researchers from the University of Kinshasa found that a quarter of respondents doubted the existence of COVID-19. 

However, 55,9% were prepared to be vaccinated. Among the 1821 participants not willing to receive a COVID-19 vaccine, the majority (60.6%) indicated they did not trust the vaccine. Some also believed it had been made to kill Africans (14,4%) or to sterilise people(5.9%).

SMS campaign to promote vaccines

A COVID-19 vaccination site in the Democratic Republic of Congo.

Overall, immunisation in the DRC is low even for well-established diseases, according to WHO and UNICEF. In 2019, 57% of people were vaccinated against Hepatitis B, 73% had the BCG vaccine against tuberculosis and only 59% had been vaccinated against polio.

UNICEF ascribes the low vaccine uptake to “chronic poverty, limited essential service infrastructure, disease outbreaks, recurrent armed conflict, massive displacement and the lack of a steady supply of vaccine doses”.

To address this, UNICEF and partners – including the mobile network operators Orange, Vodacom and Africell – launched an SMS campaign in late 2021 to support the COVID-19 vaccination campaign.

To start with, 16 million people in 15 priority provinces were sent messages encouraging them to get vaccinated by registering online by SMSing a toll-free number where they would get instructions in five main local languages. 

After four weeks, 54,000 people had registered and the government was able to prioritise delivery to areas where there is strong interest in getting vaccinated.

Bad history with COVID vaccine supply

But the DRC’s history with COVID-19 vaccines has been fraught from the start, and the supply chain problems affecting COVAX, the global vaccine access platform, did not help.

Within a month of getting 1.7 million Astra Zeneca vaccines from COVAX in March last year, the DRC stopped its vaccine rollout over concerns about blood clots. Three-quarters of these vaccines were then redeployed to other African countries to prevent them from expiring. 

But once concerns about blood clots had been addressed (found to be a rare risk outweighed by benefits), COVAX’s supply chain had dried up as India had halted the export of AstraZeneca vaccines manufactured by the Serum Institute of India, COVAX’s main supplier. 

The lack of a reliable supply of vaccines made it hard for the DRC to plan a rollout or prepare people for their arrival.

Now that a reliable stream of vaccines is available through COVAX, the DRC government is trying to speed up its vaccination programme but it has a lot of lost ground to catch up.

“Our objective is to enable 50 million Congolese to receive the vaccine by the end of 2022 and thus be better protected against the disease,” says Elisabeth Mukamba, director ot the Expanded Program on Immunization. “This innovative SMS pre-registration initiative is welcome and allows us to communicate more quickly and effectively, even in the most remote communities.”

Image Credits: Christian Mokili/ UNICEF, Gavi/2021/STARRY.

COVID-19 cases have surged to their highest in nearly two years in China.

COVID-19 cases reached their highest level in nearly two years in China on Sunday, with 1,437 cases on the mainland, according to China’s National Health Commission.

Cases have more than doubled since 10 March when 588 cases were recorded. This surge in cases, driven by the Omicron variant, has prompted the country, which has a strict zero-COVID policy, to impose fresh restrictions in provinces with a high infection rates.

It has already shutdown Jilin province which reported 895 cases on 13 March, and the mayors of Jilin city and the Jiutai district of the city of Changchun have been dismissed owing to the outbreak, according to a state-run news agency.

China has also imposed stricter restrictions on two other cities last week– Shenzhen and Shanghai. Shenzhen, which borders Hong Kong and is known to be a major hub for electrical manufacturing, is under a seven-day complete lockdown. The city, which has a population of 17.5 million people, has been brought to a complete standstill with businesses suspending operations, and public transportation halting their operations. 

According to one of China’s leading infectious disease experts, Zhang Wenhong,the domestic epidemic in China is “currently in the early stage of an exponential rise”.

He wrote on China’s microblogging site, Weibo, that if China opens up quickly now, it will cause infection of a large number of people in a short period of time. “Even a low case fatality rate will cause a run on medical resources and a short-term shock in social life, causing irreparable damage to society and families,” he said. 

Hong Kong’s high death rate

In the last 24 hours, Hong Kong reported 13,332 local cases had been diagnosed with Nucleic Acid Amplification Tests (most commonly PCR tests), while 19,095 fresh cases had been detected using the rapid antigen tests.

However, Hong Kong Leader Carrie Lam told a daily briefing that there were no plans to tighten the social distancing measures owing to the limited scope offered by the current measures in place. The country has so far witnessed 263,411 cases.

Hong Kong, like China, has a zero-COVID policy. Currently, it is compulsory to wear masks everywhere, no gatherings of more than two people are allowed, and schools and public venues are closed. 

While the former British colony has been struggling to manage an influx of patients at its hospitals, Hong Kong is slowly seeing a slowdown in the daily infection rate

According to Bloomberg, Hong Kong has registered the most deaths per million people globally in the week to 10 March. Some 286 deaths were reported on Monday. This takes the death toll to 43,279.

Meanwhile, Hong Kong opened its fourth community isolation facility on 13 March with over 1,000 beds and the region has also been working with the mainland authorities to build 90,000 isolation units to accommodate patients with mild or no symptoms, reports Reuters.

Low vaccination to blame 

Lam has blamed the low vaccination rate in Hong Kong as a factor in the high rate of deaths and infections.

“We have spent over one year to promote, encourage, coerce people to take the jab. But unfortunately, the entire society partly because of the low infection rate in the last year or so and partly because of anxiety and worries and so on, we have not achieved this high rate of vaccination, especially among the elderly,” Lam said at a press conference on Monday.

According to Hong Kong’s Department of Health, 89% of those who died in the fifth wave of Covid-19 had not received any dose of vaccination. 

Wenhong said that China must start implementing more complete, smart, and sustainable coping strategies like booster shots for the elderly and improved vaccination strategies, widely available oral drugs, affordable and widely available home testing kits, effectively trained and rehearsed hierarchical diagnosis and treatment strategies, along with better home isolation process. 

Image Credits: Flickr.

The mRNA vaccines (administered above) don’t affect fertility treatment for women or men.

The mRNA-based COVID-19 vaccines do not harm in vitro fertilization (IVF) success rates, according to a recent study, countering disinformation that vaccines could negatively affect fertility.

In contrast, the SARS-CoV2 virus has been found to negatively affect the quality of embryos for couples who are undergoing IVF treatments and sperm.

The peer-reviewed study, published in the journal Fertility and Sterility, involved 428 women aged up to 38 years of age – some vaccinated and some not – between January and August 2021. In total, the women went through 672 embryo transfers and around a quarter (23% to 26%) of the transfers led to pregnancies in all cases, regardless of whether the women were vaccinated or had been infected with COVID-19.

The study group was composed of 141 women either vaccinated with two mRNA coronavirus vaccines or recovered from the virus, and therefore all with COVID antibodies.

“One of the concerns raised by women of childbearing age around the world since the introduction of the coronavirus vaccine was that it could negatively impact IVF treatments,” said Prof Raoul Orvieto, director of Sheba Medical Center’s Infertility and IVF Institute in Israel.

“Many concerned women and mothers have approached us on this issue. This groundbreaking study shows that the vaccine does not affect a woman’s chance of getting pregnant using the frozen embryo transfer method.”

Early on in the pandemic, studies showed that pregnant women were at higher risk of developing severe COVID-19. As such, it was recommended by the World Health Organization that pregnant women get the jab. However, many women have hesitated, likely due to lack of information or misinformation about the safety of vaccines on fertility and foetuses.

“Unfounded claims in popular media linked a possible correlation between the SARS-CoV-2 vaccine and potential infertility,” the authors wrote in the study. “Such false claims by anti-vaccine activists aim to incite fear and deter public opinion from vaccination, so jeopardizing the vaccination plan and the end of the pandemic.

“Our results refute such claims and strengthen the notion that the SARS-CoV-2 vaccine is safe and should be recommended to fertility-seeking couples,” the authors continued.

Multiple studies, one result

There has been a range of recent studies examining the impact of COVID-19 and COVID-19 vaccines on fertility in both men and women.

A study published in the medical journal Reproductive Biology and Endocrinology in May 2021 proved that there was no difference in ovarian stimulation and embryological variables during IVF cycles conducted before and after receiving the Pfizer vaccine.

A separate study of 129 women published in the medical journal Human Reproduction suggested that the Pfizer COVID-19 vaccine has no negative effect on a woman’s ovarian reserve. Women’s Anti-Müllerian hormone (AMH) levels were tested before they received their first shot of the vaccines. They received the second dose three weeks later and then were tested again three months after that. AMH levels were unchanged while COVID-19 antibody levels climbed.

Finally, two separate studies examining the impact of the Pfizer vaccine on male sperm showed that it does not have an impact. In a study of 43 male patients undergoing in vitro fertilization between February and March 2021, the sperm of each subject was examined against itself before and after vaccination, and researchers saw no difference in the sperm parameters.

A team of researchers from the University of Miami also studied semen volume, sperm concentration and total amount of moving sperm. In their study, published in the JAMA journal in June, they found no declines in any of the parameters after vaccination.

“In this study of sperm parameters before and after two doses of a COVID-19 mRNA vaccine, there were no significant decreases in any sperm parameter among this small cohort of healthy men,” the study’s authors wrote. “Because the vaccines contain mRNA and not the live virus, it is unlikely that the vaccine would affect sperm parameters.”

“There is nothing we have seen to suggest any negative impact on fertility at all,” Orvieto told Health Policy Watch.

But COVID-19 can harm fertility

Orvieto said that in his first study, he looked at IVF before and after infection. While there was no direct effect on the IVF outcome, the virus did affect the ratio of top-quality embryos for up to three months after disease. In the first three months, only around 30% of embryos were top quality compared to 60% before or after that period.

“The production of eggs and sperm lasts for around three months and can be hampered by inflammatory responses, like the ones that occur as a result of a viral infection, which is the case with COVID-19,” Orvieto said. “Our study indicated that the quality of embryos producers during an IVF procedure for a couple in which one of the partners had previously contracted COVID-19 was significantly lower, and lead to a lower chance of successful implantation.”

He told Health Policy Watch that he would recommend couples wait three months after one of the partners’ had contracted COVID-10 before IVF treatments.

Other studies found up to a 50% decrease in sperm volume, concentration and motility in patients with moderate disease even 30 days post diagnosis. And there have been reports of up to 25% of men who have had COVID-19 having a sperm impairment from the disease.

“If couples are choosing not to vaccinate it is because they are reading fake news,” Orvieto said.

He added that his team has gathered what is believes to be all the information needed now to justify vaccination for fertile men and women now. The next thing would be to wait three or four years and see if there are any long-term effects of vaccination or infection on fertility.

Image Credits: Wish FM Radio.